Background: Corneal wound healing involves several biological processes, various cytokines and growth factors are released in reaction to tissue damage, including Fibroblast Growth Factor (FGF), Transforming Growth Factor (TGF), Platelet-Derived Growth Factor (PDGF), and Vascular Endothelial Growth Factor ( VEGF). VEGF is proinflammatory cytokines that increase microvascular permeability and plays an essential role in forming new blood vessels in the wound healing process. New blood vessels formed during the healing process can turn into pathological blood vessels, causing metabolic disorders in the cornea, resulting in corneal clouding and blindness. Keratoplasty is the primary therapeutic modality to replace pathological corneal tissue. Due to the limited availability of donors, many alternative therapies have been developed to restore corneal regeneration, one of which is using biomaterials in prosthetic devices with composite materials. Collagen-chitosan-natrium hyaluronate composite is a natural biopolymer considered to have good biocompatibility, biodegradable, and non-toxic properties. Besides being easy to get and produce, the composite is safe and improves corneal tissue regeneration. Methods: Twenty adults New Zealand male white rabbits (30 eyes) were divided into three groups. The first group is the negative control group, without any treatment. The positive control group was the rabbits who had injuries to the stromal layer of the cornea, and the third group was the implant group, which were rabbits who received collagen-chitosan-natrium hyaluronate composite implants after their corneal stromal was injured. On day 14, rabbits were enucleated, and the corneal tissue was examined for immunohistochemistry using anti-VEGF antibodies. Results: The study results showed a significant difference in the percentage of VEGF expression in the positive control group with the implant group was significantly different (p = 0.000, ?> 0.05). High VEGF protein expression did not exceed the positive control group indicating that the wound healing process is ongoing. Conclusion: There was a significant difference in the level of VEGF protein expression between negative control group, positive control group, and implant group. The VEGF level in the implant group was lower than in the positive control group.

cornea; biomaterials; composites; collagen; chitosan; natrium hyaluronate; VEGF; wound healing.